［原著］Elevation of intracellular CAMP inhibited cell proliferation and migration induced by platelet-derived growth factor in cultured rat vascular smooth muscle cells

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We investigated whether elevation of intracellular cyclic nucleotides (cAMP and cGMP) inhibit cell proliferation and migration of cultured embryonic rat aortic vascular smooth muscle (VSM) cells (A7r5). After treatment with drugs for up to 120 h, cell proliferation and migration were measured by adding WST-1 reagent and by counting migrated cells through the pores of cell culture insert (8-$ \mu $ pore size) , respectively. Cell proliferation was significantly inhibited by dibutyryl cAMP (db-cAMP) in a time- and concentration-dependent manner (0.03 to 3 mM) , whereas dibutyryl cGMP (db-cGMP, 3 mM) had no effect. Olprmone hydrochloride (OPN, 1 mM) , type 3 phosphodiesterase inhibitor, inhibited cell proliferation, and synergistically inhibited in the presence of db-cAMP (0.3 mM). Cell migration was significantly inhibited by treatment with db-cAMP (3 mM), but not by db-cGMP (3 mM). Combination of db-cAMP (0.3 to 3 mM) with OPN (1 mM) or forskolin (FSK) (0.1 mM) significantly inhibited cell migration after 72-htreatment. Plateletderived growth factor ( PDGF) -BB significantly stimulated cell proliferation and migration in serum-free culture condition. Treatment of the cells with db-cAMP, OPN or FSK significantly inhibited the stimulatory effect of PDGF-BB on proliferation and migration. Thus, elevation of cAMP inhibited serum stimulated and PDGF-BB induced cell proliferation and migration of A7r5 cells.

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